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Biomedical subjects

B Gerdin

Publications and source records attributed to B Gerdin.

At least 145 records · Page 8Linked to original sources
PubMed1985

The role of polymorphonuclear leucocytes in the pulmonary dysfunction induced by complement activation.

To determine the role of polymorphonuclear leucocytes (PMNs) in the pulmonary reaction induced by complement activation, pigs were infused with complement-activated plasma (CAP), cell-free supernatant from PMNs activated in vitro, or washed PMN aggregates produced in vitro. Infusion of CAP resulted in transient peripheral leucopenia, a reversible rise in pulmonary vascular resistance (PVR) and decreased arterial oxygen tension (PaO2). Indomethacin did not influence the CAP-induced drop in PMN count or the accumulation of PMNs in the lung, but significantly counteracted the rise in PVR and fall in PaO2. Antihistamines did not prevent the cellular or pulmonary reactions to CAP infusion. Methylprednisolone did not inhibit the decrease in PMN count, but modified the pulmonary reaction to CAP, although it did not prevent the rise in PVR to the same extent as indomethacin; it counteracted the fall in PaO2. Infusion of supernatant from activated PMNs did not influence the PMN count, but caused a reversible increase in PVR and a drop in PaO2. Indomethacin counteracted the pulmonary reaction to this infusion. Infusion of washed PMN aggregates did not result in any cellular or physiological changes. These findings suggest that the pulmonary reaction induced by complement activation is mediated by humoral components generated and/or released during activation of PMNs. Arachidonic acid metabolites play an important role and it is likely that substance(s) released from activated PMNs trigger prostanoid synthesis in other cells. It is conceivable, however, that PMNs exposed to activated complement factors also directly synthesize and release arachidonic acid metabolites.

Animals↗
PubMed1985

A porcine model of early adult respiratory distress syndrome induced by endotoxaemia.

To study the pathophysiology of early adult respiratory distress syndrome (ARDS) induced by sepsis, spontaneously breathing pigs under ketamine anaesthesia were investigated. Twenty animals were infused i.v. with E. coli endotoxin (10 micrograms . h-1 . kg-1) over 6 h, and ten control animals received physiological saline. In the controls, cardiac output (Qt) and O2 delivery decreased slightly. There were no changes in pulmonary gas exchange, pulmonary haemodynamics or extravascular lung water (EVLW). The polymorphonuclear (PMN) leucocyte count gradually increased, while the platelet count decreased slightly. Endotoxin infusion caused profound deterioration of pulmonary gas exchange, a marked rise in pulmonary vascular resistance (PVR) and a moderate increase in EVLW. The pulmonary dysfunction was not attributable to the pulmonary oedema per se, whereas a "dry" ventilation/perfusion inequality played an important role. The "responders" (peak venous admixture greater than 20%; n = 14) were characterized by higher Qt and lower PVR than the "non-responders". Qt declined progressively, especially in non-survivors. O2 delivery decreased considerably. Metabolic acidosis probably indicated oxygen deficit. Eleven of 20 animals died during the observation period. Mortality was related more to the imbalance between O2 delivery and oxygen demand than to the deterioration in pulmonary gas exchange. The PMN count decreased markedly while the gradual decline in platelet count was similar to that in the controls. Lung microscopy revealed PMN accumulation in the microvasculature, moderate interstitial oedema and microvascular blood stasis. Our porcine model, which closely mimics early ARDS in man, will be useful in further studies of the pathophysiological pathways and the treatment of this syndrome.

Acid-Base Equilibrium↗
PubMed1985

Prophylactic and delayed treatment with high-dose methylprednisolone in a porcine model of early ARDS induced by endotoxaemia.

The effects of prophylactic and delayed treatment with high-dose methylprednisolone were evaluated in a porcine model of early adult respiratory distress syndrome induced by endotoxaemia. Spontaneously breathing pigs under ketamine anaesthesia were infused i.v. with E. coli endotoxin (10 micrograms . h-1 . kg-1) over 6h. Twenty animals received endotoxin without treatment. Eight animals were pretreated with methylprednisolone i.v., 60 mg . kg-1, followed by an i.v. infusion at a rate of 10 mg . h-1 . kg-1. Ten animals received the same dosage of methylprednisolone beginning 2 h after the start of endotoxin infusion. Pretreatment with methylprednisolone prevented the endotoxin-induced impairment in pulmonary gas exchange and the development of pulmonary oedema. The pulmonary hypertension was counteracted. Cardiac output (Qt) and O2 delivery were improved. Mean arterial blood pressure (MAP) increased and was higher than in the untreated endotoxin group. The profound fall in PMN count was inhibited, while the accumulation of these cells in the lung was still substantial. Survival was improved. Delayed methylprednisolone treatment prevented further deterioration in pulmonary gas exchange and tended to restore it towards baseline. The pulmonary oedema and pulmonary hypertension were reduced. Qt and O2 delivery did not improve. MAP was higher than in the untreated endotoxin group towards the end of the observation period. The decline in PMN count and the pulmonary accumulation of these cells were not significantly influenced. Survival was improved. These results indicate that high-dose methylprednisolone, when given early in the course of sepsis, might be of clinical value in prevention of the devastating pulmonary and circulatory complications of this disease.

Animals↗
PubMed1985

Spontaneous scrotal emphysema--a cause of scrotal swelling.

Scrotal emphysema developed in a 24-year-old man without any sign of infection and without any trauma involved. The condition gradually improved over a few days and at follow-up one week later he was back to his normal state. No clue to the cause was found and it is therefore justifiable to claim that the patient has a 'spontaneous scrotal emphysema'.

Adult↗
PubMed1985

Suppression of cell-mediated immune reactivity by peptides cleaved from human fibrinogen.

Peptides derived from fibrinogen, known from earlier studies to inhibit the stimulation of lymphocytes in vitro and to suppress the humoral immune response in vivo, were investigated for their effect on cell-mediated immune reactivity in mice. An unfractioned mixture of peptides with molecular weights under 3,500 injected intraperitoneally at repeated intervals suppressed the contact hypersensitivity to oxazolone but did not influence the skin inflammatory reaction to croton oil. Local injections of peptides had a stronger effect on contact hypersensitivity. Four 200 micrograms local injections of peptides prior to sensitization abolished the increase in lymph node weight and the uptake of 125I-iododeoxyuridine in the draining lymph node after sensitization. Three previously isolated peptides with vasoactive effects inhibited Con A-stimulated incorporation of 3H-thymidine into spleen cells. The first, a pentapeptide (Ala-Arg-Pro-Ala-Lys), and the second, an undecapeptide (Ser-Glu-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys) both with an enhancing effect on microvascular permeability, were more potent than the third, a pentapeptide with slight vasoconstrictive properties (Thr-Ser-Glu-Val-Lys). Cell viability was not altered, as measured by trypan blue exclusion and the release of 86Rb. Accumulating evidence indicates that peptides derived from fibrin may be of importance as modulators of cellular immunoreactivity in a number of clinical conditions.

Animals↗
PubMed1985

Blockade of histamine receptors and thrombin-induced microembolic pulmonary edema in the rat.

Pulmonary edema was induced by an intravenous infusion of bovine thrombin, 500 NIH/kg b.w., given in 5 min, in rats in which fibrinolysis had been inhibited by an intraperitoneal injection of the fibrinolysis inhibitor AMCA. Ninety minutes after termination of the thrombin infusion the lung weight was increased from 1.09 +/- 0.07 to 3.14 +/- 0.12 g due to edema. A high albumin concentration in the extravascular water indicated that the edema was a consequence of increased permeability in the microcirculation. In rats injected with the H1 histamine receptor antagonist mepyramine maleate and H2 receptor antagonist cimetidine after the thrombin infusion, the lung weight was significantly lower at 90 min (2.68 +/- 0.33 g), and the amount of edema as calculated morphometrically was slightly but significantly reduced. The concentration of albumin in the extravascular water (i.e. in the edema fluid) in rats subjected to histamine receptor blockade was unchanged, indicating that the slight decrease in edema was a result of decreased filtration pressure and not of an effect on microvascular permeability.

Albumins↗
PubMed1985

Selective tissue accumulation of manganese and its effect on regional blood flow and haemodynamics after intravenous infusion of its chloride salt in the rat.

Manganese chloride (MnCl2), with or without the addition of trace amounts of 54Mn2+, was administered as a 7-min i.v. infusion in rats. Tissue accumulation of 54Mn2+ was determined 0-15 min after the infusion, and cardiac output, regional blood flows and vascular resistances were measured 5 and 60 min after the infusion by the microsphere technique. The plasma half-life of 54Mn2+ was found to be 4.7 min. Mn2+ accumulated in several organs, the highest relative concentrations being seen in the liver, duodenum, jejunum, kidney and heart, and intermediate concentrations in the ileum, colon, stomach and spleen. There was no uptake in the lung, skeletal muscle or brain. During the infusion of 180 mumol/kg b.w. of Mn2+, the arterial blood pressure fell from a mean of 123 +/- 5 mm Hg to a minimum of 85 +/- 7 mm Hg, and thereafter returned to normal. Five minutes after termination of the infusion, there was a decrease in cardiac output and minute work but not in total peripheral resistance, a finding interpreted as a negative inotropic effect of Mn2+. At this time blood flow was decreased in the stomach, ileum, colon, spleen and skin, and increased in duodenum, jejunum and liver. The blood flows were normalized 60 min after termination of the infusion in all organs except the liver and heart. The effects are probably due to the calcium-antagonistic properties of Mn2+ and the tissue accumulation is most probably a result of intracellular accumulation through calcium channels. The relation between tissue accumulation and tissue selectivity of blood-flow alterations is unexplained.

Animals↗
PubMed1984

The inflammatory reaction in an experimental model of open wounds in the rat. The effect of arachidonic acid metabolites.

The study concerned the effect of arachidonic acid metabolites on the inflammatory reaction in granulation tissue of open wounds in rats. Metabolites or inhibitors were applied in a wound chamber attached to circular, open, full-thickness skin wounds 5 days post-wounding. The adjacent wound served as control. Blood flow, albumin extravasation and accumulation of polymorphonuclear leucocytes (PMNLs) were measured in the granulation tissue. Prostaglandin E2 (PGE2 5.7 microM) increased blood flow and albumin extravasation by 95 and 16%, respectively, without affecting PMNLs. Leukotriene B4 (LTB4 2.7 microM) increased PMNL accumulation by 142% without altering albumin extravasation. Indomethacin (28 microM, repeatedly) did not affect blood flow or albumin extravasation, but increased PMNL accumulation by 21%. Methylprednisolone (3.3 mM, repeatedly) reduced blood flow and albumin extravasation by 29 and 31%, respectively, without influencing PMNLs. The granulation tissue obviously responds to exogenous PGE2 and LTB4. Endogenous arachidonic acid metabolites seem to play only a minor role in the inflammatory process in this model.

Animals↗
PubMed1984

Assessment of lung water content by roentgen videodensitometry.

In 17 anesthetized and mechanically ventilated pigs, different degrees of lung injury were induced by iv infusion of oleic acid (mean dose 0.1 ml/kg). The change in radiologic density of the chest was measured by a videodensitometer before and 4 h after oleic acid infusion. The lungs were then removed for determination of the wet/dry weight ratio (WW/DW). The change in radiologic density was significantly correlated to WW/DW (r = .87) and to the changes in end-inspiratory pressure (r = .80), mean pulmonary arterial pressure (r = .77) and venous admixture (r = .79), but not to changes in the oncotic-hydrostatic pressure gradient of the lungs (r = .46). Roentgen videodensitometry appears to be a useful method for assessing changes in extravascular lung water content.

Absorptiometry, Photon↗
PubMed1984

Complement activation and its relationship to adult respiratory distress syndrome. An experimental study in pigs.

Pulmonary leucostasis induced by complement activation has been considered an important pathogenic factor in adult respiratory distress syndrome (ARDS). To determine whether complement activation per se could evoke pulmonary dysfunction similar to ARDS, pigs were repeatedly infused with complement-activated plasma (CAP). Complement activation was produced by incubation of plasma with zymosan. Three groups of animals were investigated. Control animals received non-activated plasma. Nine animals (Group II) were given four infusions of CAP at a rate of 7 ml X min-1, and another nine animals (Group III) received two CAP infusions at a rate of 7 ml X min-1 followed by two at a rate of 14 ml X min-1. In the control animals there were no changes in gas exchange or haemodynamic variables and the leucocyte counts gradually increased. Infusion of CAP resulted in transient peripheral leucopenia and a dose-rate-dependent reversible increase in pulmonary vascular resistance in all animals. In one animal of Group II and in six of Group III there was a significant infusion-related decrease in Pao2 due to increased venous admixture. These animals were characterized by an enhanced pulmonary vascular tone before the start of the first CAP infusion. They also displayed a more pronounced pulmonary vascular response to infusion of CAP. The changes in gas exchange variables and pulmonary haemodynamics showed no relation to the degree of leucopenia or decrease in platelet count. The increased venous admixture was caused by "dry" ventilation/perfusion mismatching and not by oedema. These results suggest that additional factors besides complement activation and pulmonary leucostasis are required for the development of increased microvascular permeability and the pulmonary oedema characterizing ARDS.

Animals↗
PubMed1984

The role of histamine and serotonin in the inflammatory reaction in an experimental model of open wounds in the rat.

The role of histamine and serotonin in the inflammatory reaction in the granulation tissue of open wounds in the rat was studied. The model involved plastic chambers attached to the edges of two open circular full-thickness skin wounds. Five days post-wounding, agonists or antagonists were applied in one of the two chambers, the adjacent wound serving as control. Thereafter blood flow and albumin extravasation were measured. Application of histamine (100 microM) caused an increase in granulation tissue blood flow by 36%, but left albumin extravasation unaffected. Treatment with mepyramine (H1 antagonist, 20 microM), cimetidine (H2 antagonist, 20 microM) or methysergide (serotonin antagonist, 20 microM) did not influence the level of either blood flow or albumin extravasation. It is suggested that endogeneous histamine and serotonin play a minor role in the inflammatory process in the granulation tissue of this model of healing wounds.

Animals↗
PubMed1984

Effect of methysergide pretreatment on thrombin-induced pulmonary oedema in the rat.

Microembolic pulmonary oedema was induced by injection of thrombin (500 NIH units/kg body weight) i.v. in rats in which fibrinolysis had been inhibited by pretreatment with trans-4-aminomethyl-cyclohexanoid-carboxylic acid (AMCA). To evaluate the role of serotonin in this condition the effect of pretreatment with the antiserotonin compound methysergide (2.5 mg/kg body weight) on the amount of pulmonary oedema was studied. Pretreatment with methysergide resulted in a 20% decrease in lung weight in thrombin-treated rats. It caused a significant reduction of dilated lymph vessels, and of interstitial and alveolar oedema, as evaluated morphometrically. Methysergide pretreatment did not significantly alter the number of degranulated mast cells. Antiserotonin is thought to exert its effect by lowering the filtration pressure in the pulmonary microcirculation.

Animals↗
PubMed1984

The inflammatory reaction in healing wounds: the role of polymorphonuclear leucocytes.

The inflammatory process in granulation tissue in full-thickness skin wounds was studied and the role of polymorphonuclear leucocytes (PMNLs) in this process evaluated in an experimental model in the rat. The number of PMNLs in the wound, assessed by determination of the PMNL-specific enzyme myeloperoxidase (MPO) activity in wound exudate, increased from 0.45 U/ml on day 1 after wounding to 0.8 U/ml on day 2, and then remained constant throughout the five days of observation. The concentration of prostaglandin E2 (PGE2) in wound exudate increased progressively from 70 ng/ml on day 1 to 290 ng/ml on day 5. The lack of correlation between these two variables indicated that PMNLs were not the major source of PGE2. Blood flow and albumin extravasation in the granulation tissue were measured, and the relation between these two variables and PMNL accumulation was studied. Rats were rendered neutropenic with an antineutrophil serum, resulting in an 83% decrease in circulating PMNLs and a 61% decrease in granulation tissue MPO activity on day 5, as compared with rats treated with normal rabbit serum. These reductions did not, however, affect either blood flow or albumin extravasation, and no correlation was observed; but when inter-individual variations in the absolute levels of the variables measured were eliminated by calculating in each rat a left-to-right wound ratio, PMNL accumulation correlated well to both blood flow (R = 0.81) and albumin extravasation (R = 0.65). It is suggested that blood flow and albumin extravasation in the granulation tissue are influenced by local PMNL accumulation and, further, that the inflammatory response varies considerably between one animal and another.

Animals↗
PubMed1984

Inflammatory reaction in an experimental model of open wounds in the rat. The role of polymorphonuclear leukocytes.

The accumulation of polymorphonuclear leukocytes (PMNLs) and the concentration of prostaglandin E2 in full thickness open skin wounds, created in the back of the rat, were studied. The quantity of PMNLs in the granulation tissue, assessed by analysis of wound exudate myeloperoxidase activity, increased from 0.45 units/ml on day 1 after wounding to 0.8 units/ml on day 2 and then remained constant throughout the 5 days of observation. The prostaglandin E2 concentration in wound exudate was measured by radioimmunoassay increased progressively from 70 ng/ml on day 1 to 290 ng/ml on day 5. The lack of correlation between these two variables indicates that PMNLs were not the major source of prostaglandin E2. To study the relation between PMNL accumulation, blood flow, and albumin extravasation in the granulation tissue, rats were treated with an antineutrophil serum. This resulted in an 83% decrease in circulating PMNLs and a 61% decrease in granulation tissue myeloperoxidase activity on the 5th day, as compared with rats treated with normal rabbit serum. No relationship was observed between myeloperoxidase activity and blood flow (r = 0.37) or between myeloperoxidase activity and albumin extravasation (r = -0.34) when absolute values were compared. However, when interindividual variation in the absolute levels of the variable measured was eliminated, by calculating in each rat a left to right wound ratio, good correlations (r = 0.81 and r = 0.65, respectively) were found. It is suggested that blood flow and albumin extravasation in the granulation tissue are influenced by local PMNL accumulation.

Animals↗
PubMed1983

Structural requirements for microvascular permeability-increasing ability of peptides. Studies on analogues of a fibrinogen pentapeptide fragment.

A pentapeptide, Ala-Arg-Pro-Ala-Lys, liberated from fibrinogen during plasmin-mediated fibrinolysis, was shown earlier to increase microvascular permeability in rat and human skin. Eighteen new analogues have now been synthesized in addition to the 15 previously prepared and examined for their effect on permeability. The old concept that a tetrapeptide with basic amino acids at both ends and a proline residue adjacent to the N-terminal amino acid is essential for high activity on permeability, has now been challenged. The results obtained with several of the new analogues strengthen this concept. More interestingly, however, the third amino acid, which was found in earlier studies to be less sensitive to exchange, has now been deleted as well as duplicated with only a modest loss of activity of the peptide. The chirality of the C-terminal amino acid, most surprisingly, does not seem to be crucial for peptide activity. Slightly superpotent analogues were obtained on amidation of the C-terminus. In addition, a few naturally occurring peptides, namely tuftsin, substance P, neurotensin and bradykinin, the amino acid sequences of which all exhibit characteristic features of some of our active peptide analogues were investigated in the same test system. Tuftsin displayed a potency equal to that of the pentapeptide. The other three peptides were all highly superpotent in this assay system.

Animals↗
PubMed1983

Effects of peptides cleaved from human fibrinogen by plasmin on rabbit kidney cells in culture.

Low molecular weight fibrinogen degradation products (LMW-FDP) containing a mixture of dialysable peptides cleaved from human fibrinogen by plasmin are cytotoxic to an established line of rabbit kidney cells and to primary cultures of rabbit kidney cells. The presence of LMW-FDP in a concentration of 50 micrograms/ml during the cell cultivation caused a considerable release of 51Cr from prelabelled cells and inhibited 3H-thymidine and 86Rb uptake. Among three isolated peptides of established primary structure only one, 6D: Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys, induced a significant effect, i.e. it enhanced 3H-thymidine incorporation. Two others, 6A: Ala-Arg-Pro-Ala-Lys and 6E: Thr-Ser-Glu-Val-Lys, did not influence the examined parameters. Hence other components of LMW-FDP must be assumed to be responsible for the cytotoxic effect on kidney cell cultures.

Animals↗